This laboratory is evaluating phosphorothioate deoxyribonucleic acids (DNAs) and peptide nucleic acids (PNAs) for a variety of nuclear medicine applications. Morpholinos (MORFs) are a new class of oligomers with a nuclease-resistant, nonionic and water-soluble phosphorodiamidate backbone. We now report on the in vitro and in vivo properties of MORFs labeled with technetium-99m. Both 15-mer and 18-mer MORFs were obtained, each with a primary amine attached to the 3' equivalent end via a three-carbon beta-alanine linker. The amine was used to conjugate with NHS-MAG3 for 99mTc radiolabeling. By surface plasmon resonance at room temperature, the association rate constant for hybridization of the 18-mer MORF to its complementary oligomer (cMORF) was equivalent to that of DNAs and PNAs of comparable length. Hybridization of 99mTc-MORF in vitro to free cMORF, to a cMORF polymer and to cMORF beads was nearly quantitative under a variety of conditions. Kinetic studies in vitro at room temperature showed rapid (2-5 min) and nearly quantitative (90%) binding to cMORF beads. Using size-exclusion high-performance liquid chromatography, the stability of the 99mTc-MORF was found to be greater than 85% over 24 h in 37 degrees C serum with minimal protein binding. In normal mice, the 99mTc-MORF showed rapid pharmacokinetics, with only 21% and 8% remaining in the whole body at 3 and 24 h post administration, respectively. In vivo targeting with 99mTc-MORF of cMORF beads in one thigh of normal mice compared to control beads in the other thigh showed target/control thigh ratios of 2-10 between 3 and 24 h. These results demonstrate that MORF oligomers are capable of in vivo hybridization. Their properties of hybridization affinity and kinetics and their in vivo stability and pharmacokinetics make them suitable subjects for in vivo studies.
It has been reported that the stability of a 1.11-GBq (30 mCi) technetium-99m d,l-hexamethyl-propylene amine oxime (HMPAO) preparation can be improved to up to 5 h by the addition of 200 micrograms CoCl2.6H2O within 2 min after reconstitution. However, it is not clear whether this method is also efficient for high-activity preparations (5.55 GBq) and whether this modified 99mTc-d,l-HMPAO has the same biological properties and can safely be used. We have now studied CoCl2-stabilised 99mTc-d,l-HMPAO preparations containing different amounts of "in-house" HMPAO ligand and SnCl2 and reconstituted with activities from 1.11 GBq to 5.55 GBq 99mTc. The characteristics of the generator eluates were also divergent, ranging from fresh eluates from a generator eluted less than 2 h previously to 4-h-old eluates from a generator not eluted during the preceding 72 h. Preparations containing up to 5.55 GBq 99mTc and as low as 2 micrograms SnCl2.2H2O can be efficiently stabilised for at least 6 h by the addition of CoCl2 shortly after reconstitution. Interestingly, it was found that the stabilisation method is not efficient if the cobalt ions are added prior to reconstitution of the preparation. This implies that the cobalt chloride cannot be incorporated in the labelling kit. Also, preparations with amounts of the ligand lower or higher than 0.5 mg formed the 99mTc-d,l-HMPAO complex with low radiochemical yield or showed rapid degradation. Therefore, combination of a subdivision and storage of Ceretec kits in fractions (as reported in the literature) is contra-indicated with this CoCl2 stabilisation method. CoCl2-stabilised Ceretec kits reconstituted with 5550 MBq 99mTcO4- and used 4-5 h after preparation retain the diagnostic usefulness of the fresh 1110-MBq preparation with regard to leucocyte labelling and brain imaging. Although baboon brain uptake of the stabilised preparation was 6%-9% lower, this small difference could not be distinguished in the tomographic images. The data obtained with both inhouse prepared d,l-HMPAO and Ceretec kits suggest that the eluate restrictions recommended by the Ceretec manufacturer can be neglected if the preparation is stabilised with Co2+ ions. Studies with 57Co-spiked CoCl2 added to d,l-HMPAO preparations demonstrated that the Co2+ ions clearly interact with the d,l-HMPAO ligand, probably to form one or more complexes. From biodistribution studies in mice it became evident that the toxicological profile of the Co2+ ions in the presence of d,l-HMPAO should be more favourable than that of cobaltous ions. For these reasons, it seems justifiable that CoCl2-stabilised 99mTc-d,l-HMPAO preparations should undergo rigorous studies to elucidate their clinical usefulness and pharmacological safety.
We are developing electron linear accelerator 100 Mo(c,n) 99 Mo technology as a replacement to nuclear reactor 235 U(n,f) 99 Mo production. We report irradiation of natural molybdenum disks (25 MeV, 10 kW) and 100 Moenriched disks (35 MeV, 2 kW), their dissolution and the extraction of 99m Tc-pertechnetate. Up to 6.2 GBq 99 Mo was produced, solvent extraction was performed at [90 % yields of 99m Tc, and quality control showed that a product with high radionuclidic and radiochemical purity could be obtained. Irradiated natural molybdenum products showed more impurities ( 91m Nb, 92m Nb, 95m Nb and 95 Nb) than enriched target material. Linear accelerator technology is feasible for production of quality 99 Mo/ 99m Tc, particularly when paired with 100 Mo-enriched targets.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.